Is there a role for academic medical centers in emerging markets?

Governments in emerging markets face mounting challenges in managing health spending, building capability and capacity, modernizing ageing infrastructure, and investing in skills and resources. One path to overcoming these challenges is to establish new public-private models of health care development and delivery based on United States academic medical centers, whose missions are to advance medical education and clinical delivery. Johns Hopkins Medicine is a participant in the collaboration developing between the Perdana University Hospital and the Perdana University Graduate School of Medicine in Malaysia. These two organizations comprise an academic health science center based on the United States model. The Perdana project provides constructive insights into the opportunities and challenges that governments, universities, and the private sector face when introducing new models of patient care that are integrated with medical education, clinical training, and biomedical research.

Poor outcomes associated with drainage of pericardial effusions in patients with pulmonary arterial hypertension.

OBJECTIVES: Pulmonary arterial hypertension (PAH) in its advanced stages is complicated by right heart failure and often pericardial effusion. The optimal treatment of large or hemodynamically significant pericardial effusions in this group has not been defined. METHODS: All patients followed at the Johns Hopkins Hospital for PAH during a 1-year period that underwent pericardiocentesis or pericardial window placement were identified. Charts were analyzed for patient characteristics, echocardiographic data, and type/outcome of procedure. RESULTS: Six patients were identified; five underwent therapeutic drainage. Pericardiocentesis was performed in four cases; two had surgical pericardial windows. Two patients died after pericardiocentesis and one patient died after surgery. All patients died within 13 hours of the procedure. CONCLUSION: We found a high mortality related to pericardial fluid drainage in patients with PAH. The pathophysiologic explanation for these deaths remains unclear, but clinicians should consider conservative management in this situation if possible.

Supramaximal inflation improves lung compliance in subjects with amyotrophic lateral sclerosis.

RATIONALE: Lung compliance has been found to be low in patients with chronic diaphragmatic weakness or paralysis but has not been well-studied in patients with amyotrophic lateral sclerosis (ALS). Noninvasive positive-pressure ventilation (NPPV) prolongs survival in ALS patients but may also have additional beneficial effects. OBJECTIVES: This study evaluated static expiratory lung compliance (CL) in subjects with ALS and determined the effect of lung inflation with supramaximal inflation on CL. DESIGN: This was a prospective trial comparing CL before and after supramaximal lung inflation via mouthpiece-delivered positive pressure. SETTING: A single university medical center with an multidisciplinary ALS center. PARTICIPANTS: Fourteen subjects with ALS were compared to 4 healthy volunteers. INTERVENTIONS: Subjects underwent a battery of pulmonary function tests including for CL. Then they used positive pressure administered via a mouthpiece set to 10 cm H2O above their maximal static recoil pressure for 5 min. The CL measurement was then repeated. RESULTS: The mean (+/- SD) baseline CL was reduced (164.1 +/- 82.1 mL/cm H2O) in subjects with ALS and was significantly lower than that in healthy volunteers (237.5 mL/cm H2O; p = 0.04). CL increased significantly in subjects with evidence of diaphragm weakness (change in CL, 11.3 +/- 16.7 mL/cm H2O; p = 0.03). Healthy volunteers did not have an increase in CL. CONCLUSIONS: Patients with ALS and diaphragmatic weakness have reduced CL, and brief supramaximal inflation increases CL. These findings suggest that atelectasis or increased alveolar surface forces are present in ALS patients and that these patients will have increased work of breathing. Some of the beneficial effects demonstrated with NPPV therapy may be through its effects on CL and the work of breathing.

Spirometry in the supine position improves the detection of diaphragmatic weakness in patients with amyotrophic lateral sclerosis.

STUDY OBJECTIVES: To determine which respiratory function tests best predicted diaphragmatic strength in patients with amyotrophic lateral sclerosis. PATIENTS AND METHODS: Patients referred for pulmonary evaluation were included (n = 25) if they underwent measurement of transdiaphragmatic pressure (Pdi) and one or more of the following on the same day: upright FVC, supine FVC, upright FEV(1), supine FEV(1), maximal inspiratory pressure (MIP), maximal expiratory pressure (MEP), and PaCO(2). Abdominal paradox and use of accessory muscles were also assessed. Bivariate analyses were performed using simple linear regression. Sensitivity and specificity of the potential predictors to detect an abnormal Pdi (< 70 cm H(2)O) were calculated. SETTING: Pulmonary function laboratory of an academic medical center. RESULTS: Upright FVC, FEV(1), and MEP were all significantly correlated with Pdi, while MIP and PaCO(2) were not. Supine FVC was the most highly correlated predictor of Pdi (R(2) = 0.76). A cutoff of supine FVC that was < 75% predicted was 100% sensitive and specific for predicting an abnormally low Pdi. Accessory muscle use and abdominal paradox were both significantly associated with Pdi, and the presence of accessory muscle use had a sensitivity of 84% and a specificity of 100% for detecting a low Pdi. CONCLUSIONS: Our findings suggest that supine FVC is an excellent and simple test of diaphragmatic weakness.

"Genes to society"--the logic and process of the new curriculum for the Johns Hopkins University School of Medicine.

In August 2009, the Johns Hopkins University School of Medicine implemented a new curriculum, "Genes to Society" (GTS), aimed at reframing the context of health and illness more broadly, to encourage students to explore the biologic properties of a patient's health within a larger, integrated system including social, cultural, psychological, and environmental variables. This approach presents the patient's phenotype as the sum of internal (genes, molecules, cells, and organs) and external (environment, family, and society) factors within a defined system. Unique genotypic and societal factors bring individuality and variability to the student's attention. GTS rejects the phenotypic dichotomy of health and illness, preferring to view patients along a phenotypic continuum from "asymptomatic and latent" to "critically ill." GTS grew out of a perceived need to reformulate the student experience to meet the oncoming revolution in medicine that recognizes individuality from the genome to the environment. This article describes the five-year planning process that included the definition of objectives, development of the new curriculum, commission of a new education building, addition of enhancements in student life and faculty development, and creation of a vertical and horizontal structure, all of which culminated in the GTS curriculum. Critical ingredients in meeting the challenges of implementing GTS were leadership support, dialogue with faculty, broad engagement of the institutional community, avoidance of tunnel vision, and the use of pilot courses to test concepts and methods. GTS can be viewed as the foundation for the scientific and clinical career development of future physicians.

Early use of non-invasive ventilation prolongs survival in subjects with ALS.

Non-invasive positive pressure ventilation (NPPV) can improve survival in ALS patients with advanced respiratory impairment, but it is not known if it is beneficial earlier in the disease course. A retrospective cohort study of patients with ALS was performed comparing survival from time of diagnosis in subjects who started NPPV use when their FVC was >or=65% predicted (Early NPPV) with subjects who started NPPV when their FVC was below 65% predicted (Standard NPPV). The Early group (n = 25) and the Standard group (n = 67) were similar except for pulmonary function (mean FVC in Early NPPV group = 74.3+/-10.1% predicted and 48.3+/-11.3 in Standard group, p<0.001). The median time from ALS diagnosis to death was significantly longer in the Early NPPV group (2.7 years vs. 1.8 years, p = 0.045). This remained significant after adjustment for potential confounding factors (H.R. = 0.55, 95% CI 0.31-0.98). Survival from time of diagnosis was nearly one year longer in the Early group. Until more definitive data are available from randomized trials, our findings suggest that clinicians either encourage earlier use of NPPV or use more sensitive tests for respiratory muscle impairment than upright FVC.

Pulmonary predictors of survival in amyotrophic lateral sclerosis: use in clinical trial design.

The rapidity of progression of amyotrophic lateral sclerosis (ALS) to death or respiratory failure impacts patients, clinicians, and clinical investigators. This study compared the abilities of various pulmonary function tests to predict tracheostomy-free survival. We evaluated 95 ALS patients by determining upright and supine forced vital capacity (FVC), maximal inspiratory (MIP) and expiratory (MEP) pressures, arterial partial pressure of carbon dioxide (PaCO2), and transdiaphragmatic sniff pressures (Pdi-sniff). Tracheostomy-free survival time was measured from the date of spirometry. Supine FVC, upright FVC, MIP, MEP, and Pdi-sniff were significantly associated with tracheostomy-free survival after controlling for nonpulmonary factors, whereas PaCO2 was not. A normal supine FVC, MIP, or MEP was highly predictive for one-year survival. These tests are well suited to predict survival for trial enrollment and patient counseling. Supine FVC's simplicity of use and availability to ALS investigators makes it a particularly attractive predictor of one-year survival in ALS.

Amyotrophic lateral sclerosis: evaluation and treatment of respiratory impairment.

Patients with amyotrophic lateral sclerosis (ALS) invariably develop respiratory muscle weakness and most die from pulmonary complications. There are numerous tests available to evaluate respiratory status in ALS and it is important to understand their various advantages and limitations. Forced vital capacity (FVC) is commonly used but can remain normal despite substantial inspiratory muscle weakness. Maximal pressures measured at the mouth are useful for excluding weakness if they are normal but are difficult to interpret if abnormal. Invasive testing, such as measurement of transdiaphragmatic pressure, provides an accurate measure of inspiratory strength but is not readily available and is not practical for serial measures. There are supportive respiratory techniques that have been shown to benefit patients with ALS. Clinicians should be familiar with these interventions, including mechanically assisted coughing, non-invasive ventilation and tracheostomy with mechanical ventilation. Observational studies have demonstrated improved survival and quality of life with noninvasive ventilation. Tracheostomy with long-term mechanical ventilation is not frequently used but can be an important component of care for ALS. This review describes an approach to respiratory evaluation and care of patients with ALS.

Use of noninvasive ventilation in patients with amyotrophic lateral sclerosis.

INTRODUCTION: Noninvasive positive pressure ventilation (NIPPV) is associated with improved survival in amyotrophic lateral sclerosis (ALS) and has been widely recommended. The extent of NIPPV use in ALS patients and the factors associated with its use have not been studied. METHODS: A cross-sectional study using the ALS Patient Care Database. Analyses were performed to assess the association of patient and care characteristics with use of ventilatory support. RESULTS: 1458 patients were studied. 15.6% used NIPPV and 2.1% used invasive mechanical ventilation. Patients who used NIPPV were significantly more likely to be male and have higher income than those who did not. They were also more likely to have a gastrostomy tube, lower vital capacity, more severe disease, bulbar involvement and poorer general health status as measured by the SF-12 and Sickness Impact Profile. Multivariate analysis revealed that lower FVC, higher income and use of gastrostomy tube were independently associated with use of NIPPV. CONCLUSIONS: NIPPV is used more than seven times as frequently as invasive ventilation in ALS patients. Patients who use NIPPV have more severe disease than those who do not use any respiratory intervention. Patients with lower income are less likely to use NIPPV, which raises concerns about disparities in the care of patients with ALS.